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p46, a novel natural killer cell-specific surface molecule that mediates cell activation.

Sivori S, Vitale M, Morelli L, Sanseverino L, Augugliaro R, Bottino C, Moretta L, Moretta A - J. Exp. Med. (1997)

Bottom Line: Upon mAb-mediated cross-linking, p46 molecules induced strong cell triggering leading to [Ca2+]i increases, lymphokine production, and cytolytic activity both in resting NK cells and NK cell clones.The p46-mediated induction of Ca2+ increases or triggering of cytolytic activity was downregulated by the simultaneous engagement of inhibitory receptors including p58, p70, and CD94/NKG2A.Both the unique cellular distribution and functional capability of p46 molecules suggest a possible role in the mechanisms of non-major histocompatibility complex-restricted cytolysis mediated by human NK cells.

View Article: PubMed Central - PubMed

Affiliation: Istituto di Istologia ed Embriologia Generale, Università di Genova, Genova, Italy.

ABSTRACT
Limited information is available on the surface molecules that are involved in natural killer (NK) cell triggering. In this study, we selected the BAB281 monoclonal antibody (mAb) on the basis of its ability to trigger NK-mediated target cell lysis. BAB281 identified a novel NK cell-specific surface molecule of 46 kD (p46) that is expressed by all resting or activated NK cells. Importantly, unlike the NK cell antigens identified so far, the expression of p46 was strictly confined to NK cells. Upon mAb-mediated cross-linking, p46 molecules induced strong cell triggering leading to [Ca2+]i increases, lymphokine production, and cytolytic activity both in resting NK cells and NK cell clones. The p46-mediated induction of Ca2+ increases or triggering of cytolytic activity was downregulated by the simultaneous engagement of inhibitory receptors including p58, p70, and CD94/NKG2A. Both the unique cellular distribution and functional capability of p46 molecules suggest a possible role in the mechanisms of non-major histocompatibility complex-restricted cytolysis mediated by human NK cells.

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Related in: MedlinePlus

Anti–p46-mediated [Ca2+]i mobilization. Clone KK26  (p46+, p58.1+, p50.3+) was analyzed for [Ca2+]i mobilization after stimulation with anti-p46 (a) or anti-p46 plus anti-p58.1 (b) mAb followed by  isotype-specific goat anti–mouse. (c and d) It is also shown that the [Ca2+]i  mobilization induced by anti-p50.3 mAb (c) can be downregulated by the  co–cross-linking of the activating molecules (p50.3) with the inhibitory  NK receptor (p58.1) (d). All the mAbs used here were of the IgG1 isotype.
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Figure 7: Anti–p46-mediated [Ca2+]i mobilization. Clone KK26 (p46+, p58.1+, p50.3+) was analyzed for [Ca2+]i mobilization after stimulation with anti-p46 (a) or anti-p46 plus anti-p58.1 (b) mAb followed by isotype-specific goat anti–mouse. (c and d) It is also shown that the [Ca2+]i mobilization induced by anti-p50.3 mAb (c) can be downregulated by the co–cross-linking of the activating molecules (p50.3) with the inhibitory NK receptor (p58.1) (d). All the mAbs used here were of the IgG1 isotype.

Mentions: In these experiments we analyzed whether NK cell triggering via p46 involved [Ca2+]i increases, similar to other triggering surface molecules expressed by NK cells (6). As shown in Fig. 7 a, a sharp [Ca2+]i increase could be detected in the representative clone KK26 (p46+, p58.1+, p50.3+) after stimulation with anti-p46 mAb. However, [Ca2+]i increments occurred only in the presence of a goat anti–mouse second reagent (i.e., in the presence of efficient cross-linking of P46 molecules).


p46, a novel natural killer cell-specific surface molecule that mediates cell activation.

Sivori S, Vitale M, Morelli L, Sanseverino L, Augugliaro R, Bottino C, Moretta L, Moretta A - J. Exp. Med. (1997)

Anti–p46-mediated [Ca2+]i mobilization. Clone KK26  (p46+, p58.1+, p50.3+) was analyzed for [Ca2+]i mobilization after stimulation with anti-p46 (a) or anti-p46 plus anti-p58.1 (b) mAb followed by  isotype-specific goat anti–mouse. (c and d) It is also shown that the [Ca2+]i  mobilization induced by anti-p50.3 mAb (c) can be downregulated by the  co–cross-linking of the activating molecules (p50.3) with the inhibitory  NK receptor (p58.1) (d). All the mAbs used here were of the IgG1 isotype.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2211712&req=5

Figure 7: Anti–p46-mediated [Ca2+]i mobilization. Clone KK26 (p46+, p58.1+, p50.3+) was analyzed for [Ca2+]i mobilization after stimulation with anti-p46 (a) or anti-p46 plus anti-p58.1 (b) mAb followed by isotype-specific goat anti–mouse. (c and d) It is also shown that the [Ca2+]i mobilization induced by anti-p50.3 mAb (c) can be downregulated by the co–cross-linking of the activating molecules (p50.3) with the inhibitory NK receptor (p58.1) (d). All the mAbs used here were of the IgG1 isotype.
Mentions: In these experiments we analyzed whether NK cell triggering via p46 involved [Ca2+]i increases, similar to other triggering surface molecules expressed by NK cells (6). As shown in Fig. 7 a, a sharp [Ca2+]i increase could be detected in the representative clone KK26 (p46+, p58.1+, p50.3+) after stimulation with anti-p46 mAb. However, [Ca2+]i increments occurred only in the presence of a goat anti–mouse second reagent (i.e., in the presence of efficient cross-linking of P46 molecules).

Bottom Line: Upon mAb-mediated cross-linking, p46 molecules induced strong cell triggering leading to [Ca2+]i increases, lymphokine production, and cytolytic activity both in resting NK cells and NK cell clones.The p46-mediated induction of Ca2+ increases or triggering of cytolytic activity was downregulated by the simultaneous engagement of inhibitory receptors including p58, p70, and CD94/NKG2A.Both the unique cellular distribution and functional capability of p46 molecules suggest a possible role in the mechanisms of non-major histocompatibility complex-restricted cytolysis mediated by human NK cells.

View Article: PubMed Central - PubMed

Affiliation: Istituto di Istologia ed Embriologia Generale, Università di Genova, Genova, Italy.

ABSTRACT
Limited information is available on the surface molecules that are involved in natural killer (NK) cell triggering. In this study, we selected the BAB281 monoclonal antibody (mAb) on the basis of its ability to trigger NK-mediated target cell lysis. BAB281 identified a novel NK cell-specific surface molecule of 46 kD (p46) that is expressed by all resting or activated NK cells. Importantly, unlike the NK cell antigens identified so far, the expression of p46 was strictly confined to NK cells. Upon mAb-mediated cross-linking, p46 molecules induced strong cell triggering leading to [Ca2+]i increases, lymphokine production, and cytolytic activity both in resting NK cells and NK cell clones. The p46-mediated induction of Ca2+ increases or triggering of cytolytic activity was downregulated by the simultaneous engagement of inhibitory receptors including p58, p70, and CD94/NKG2A. Both the unique cellular distribution and functional capability of p46 molecules suggest a possible role in the mechanisms of non-major histocompatibility complex-restricted cytolysis mediated by human NK cells.

Show MeSH
Related in: MedlinePlus